Systemic lupus erythematosus (SLE) is the prototypic systemic inflammatory autoimmune disease that affects predominantly young premenopausal women. African-American women are afflicted 3 to 4 times more frequently than Caucasian women. The risk of myocardial infarction in women with SLE is up to 50 times higher than expected in women aged 35-44 years, a population of women that should otherwise be protected from such risks. SLE presents unique challenges to studying cardiovascular disease. In SLE, there are several potential mechanisms for ischemia, such as overt vasculitis, vasospasm, microvascular disease, or thrombosis with or without atherosclerosis. Thus, one cannot assume that all ischemic events in SLE are due to atherosclerosis. We do not know the burden of atherosclerosis in SLE or the most predictive risk factors. In addition to traditional factors, inflammatory, immunological, and treatment-related factors specific to SLE are likely involved. Specifically, we plan to: (1) compare the prevalence and extent of subclinical vascular disease in 200 SLE patients and matched controls. Subclinical disease will be defined by calcification of the coronary arteries and aorta as measured by electron beam CT, and carotid plaque and intima media thickness as measured by B mode ultrasound. Patients will be recruited from the Pittsburgh Lupus Registry; (2) determine whether the risk factors associated with subclinical vascular disease in patients with SLE are different from controls. Traditional, inflammatory and immunological factors will be measured; (3) determine the risk factors associated with progression of carotid atherosclerosis over a 3-year period in women with SLE. It is important to determine the burden of atherosclerosis in this unique population, examine potential risk factors, and ultimately design intervention and prevention trials. More far reaching is that SLE may be an ideal experiment of nature' in which to further examine the role of inflammation and immune mechanisms in atherogenesis.